Figure 3.

Schematic of the interplay of natural and sexual selection acting on cell-surface sialic acids. (A) Natural selection by pathogens recognizing and exploiting Neu5Gc (blue diamond) as a receptor on host target cells can select for mutant CMAH⁽⁻⁾ alleles that abolish expression of Neu5Gc in homozygote individuals and prevent infection. Such homozygous null individuals have only Neu5Ac on their cells (red diamonds) and at higher frequencies would be targeted by other pathogens adapted or adapting to the host glycan change (magenta). This equilibrium would result in maintenance of glycan polymorphism by balancing selection. (B) Anti-Neu5Gc antibody-expressing CMAH^(−/−) females, immunized by dietary consumption of Neu5Gc rich food (red meat) or by sperm antigens containing Neu5Gc, favor loss-of-function alleles on sperm due to reproductive incompatibility with CMAH^(−/+) or CMAH^(+/+) males expressing Neu5Gc on their sperm. Once the frequency of the CMAH⁽⁻⁾ allele reaches a certain level, this process can drive the fixation of the CMAH⁽⁻⁾ allele in a population via directional selection. Figure modified from Ghaderi et al. (8).